Effects Of Nicotinamide N-Methyiltransferase(NNMT) Inhibition On The Aerobic And The Anaerobic Endurance Exercise Capacity

Background and objective:The physiological function of nicotinamide N-methyltransferase is to produce S-adenosyl-cysteine and N-methylnicotinamide from methyl donor S-adenosyl-methionine.As nicotinamide adenine dinucleotide is a key enzyme in energy metabolism,as a precursor of NAD~+,methylation of nicotinamide has a significant effect on energy metabolism.From a physiological point of view,exercise ability is related to the reproduction of ATP,the duration of supply and the operation of different energy supply systems.In our lab's early research,we found,Swimmers with higher basal metabolism rate of nicotinamide also achieved better results in short distance swimming events.The single nucleotide variation of NNMT gene had a significant effect on college students'1000 meter sports performance.In order to further study the exact role of NNMT in exercise,the activity of NNMT was inhibited by NNMT inhibitor,MNAN,and then the effects of NNMT inhibition on aerobic and anaerobic endurance were observed.Methods:Forty-eight 12-week-old male Sprague-Dawley rats were randomly divided into MNA group(n=24)and control group(n=24).The MNA group was injected with MNA(100mg/kg)three times(interval time 4 hours),and the control group injected with the same dose of normal saline.Exercise tests were conducted 2hours after the drug injection,and the effects of NNMT inhibition on lactate threshold,maximum blood lactate level,aerobic and anaerobic endurance were measured.Result:(1)When the lactate threshold appeared,there was no significant difference in the load intensity between the MNA group and the control group(the percentage of the load when the rats swim)(4.542±1.057 vs.4.646±0.900,P>0.05).When the maximum exercise intensity was reached(exhausted),there was no significant difference(6±0.807 vs.6±0.542,P>0.05).(2)the blood lactic acid level of rats in MNA group was significantly lower than that in control group after completing the maximum load swimming test.The difference was significant(P<0.01):10.402±1.386 vs 11.664±1.711 mmol/L immediately after exercise,11.489±1.378 vs12.823±1.626 mmol/L at 2 min after exercise and 12.837±1.361 vs 14.307±1.540mmol/L at 4 min after exercise.(3)in the anaerobic endurance test,the results of exercise of the rats in the above lactate threshold intensity load swimming group were significantly lower than those in the control group(P<0.05):only 8 rats in the MNA group entered the top 24,while 16 rats in the control group entered the top 24.(4)in the aerobic endurance test(the results of exercise of the rats in the Lactic acid intensity load swimming group were very close to those in the control group,there was no significant difference between the two groups(P>0.05).Conclusion:Inhibition of NNMT had a significant effect on anaerobic endurance exercises,but had no significant effect on aerobic endurance exercise ability.It shows that NNMT plays an active role in anaerobic endurance sports.This provides a physiological basis for better selection of sports materials,and also provides a theoretical basis for further study of the function of NNMT.